Mechanisms of bleeding and thrombosis in myeloproliferative disorders

Arterial and venous thromboses and microcirculatory disturbances such as erythromelalgia and neurologic and visual symptoms are the thrombotic manifestations occurring in Polycythaemia Vera and Essential Thrombocythaemia. The increased in vivo thromboxane A2 generation existing in these patients and the selective sensitivity of erythromelalgia to aspirin suggest that platelet PGG/H synthase products may be involved in transducing the increased thrombotic risk. The relationship between Thromboxane A2 production and thrombotic accidents will be investigated by the European Collaboration on Low-Dose Aspirin in Polycythaemia Vera (ECLAP) which will test the efficacy of low-dose aspirin by a randomised clinical trial. The haemorrhagic diathesis of polycythaemic and thrombocythaemic subjects is generally mild and spontaneous bleeding usually manifests in patients with very high platelet count. Its mechanism may be related to quantitative as well as to qualitative platelet changes. Possible mechanisms linking the high grade thrombocytosis to bleeding are consumption of von Willebrand factor and clot fragility due to a mechanical effect of the high platelet count or to inhibition of fibrin polymerization by platelet Glycoprotein Ib.